Antipsychotics Linked to Childhood Diabetes

Action Points

Explain that a retrospective study found that children taking second-generation antipsychotic medications had a higher incidence of diabetes than those not on any psychotropic drugs, but they did not have a significantly higher incidence compared with children taking antidepressants.

Note that the incident number of cases of diabetes in the study population was very small.

Diabetes may be substantially more likely for children taking second-generation atypical antipsychotics, according to findings from a recent study, which included a number of caveats.

Incidence of diabetes appeared to be more than four times higher among children on a second-generation antipsychotic than in those not using psychotropic medications, Susan E. Andrade, ScD, of the University of Massachusetts in Worcester, and colleagues found.

If real, the risk would pose an important drug safety and public health concern, the group noted in the December issue of Pediatrics.

Such a link may be plausible, given that the newer generation of antipsychotics is known to cause metabolic problems and weight gain in both children and adults, along with insulin resistance and diabetes in adults, they pointed out.

But the study couldn't draw any definite conclusions because of the low number of diabetes cases found.

In a retrospective administrative database analysis, just 57 diabetes cases developed among the 9,636 children ages 5 to 18 who started on a second-generation antipsychotic medication from January 2001 to December 2008.

The children were followed through medical, pharmacy, and outpatient laboratory records of three health maintenance organization plans.

The rate of incident diabetes was:

3.23 cases per 1,000 person-years in children on the antipsychotics

0.76 cases per 1,000 person-years in children not on any psychotropic medication

1.86 cases per 1,000 person-years in children on antidepressants

The incidence rate ratio for diabetes with second-generation antipsychotic use in the unadjusted analysis was 4.24-fold that of children not on psychotropics (95% confidence interval 1.95 to 8.72).

But while the association actually appeared stronger after propensity score matching, it lost statistical significance in that analysis (IRR 4.47, 95% CI 0.23 to 263.82).

Compared with children taking antidepressant medications, atypical antipsychotic use wasn't a bigger diabetes risk in either the unadjusted analysis (IRR 1.74, 95% 0.77 to 3.78) or after propensity matching (IRR 3.58, 95% CI 0.92 to 20.30).

Children on antidepressants may have been a better comparison group because they were more similar in terms of healthcare encounters with the potential for detection or diagnosis of diabetes, Andrade's group noted.

But antidepressants themselves may present a risk for diabetes, based on some recent studies, though evidence is conflicting.

"If a causal association exists between antidepressant medication use and diabetes, then the use of this comparison group might have attenuated an actual association between second-generation antipsychotic use and diabetes in the present study," the investigators wrote in the paper.

Another problem was that both adjusted analyses included fewer children on antipsychotics -- 2,531 for the comparison with no psychotropic use and 8,012 for the comparison with antidepressant use.

That further limited the statistical power, because only three and 13 diabetes cases developed in those two groups, respectively.

Too few cases were found to break out risk by the various second-generation antipsychotic medications, Andrade and colleagues noted. Nor were diabetes cases separated into type 1 and type 2 diagnoses, though any effect of antipsychotics would be expected to be on type 2 diabetes incidence.

More studies will be needed to determine whether and how much atypical antipsychotics impact diabetes among children, they concluded.

The study was supported by grant funding from the Agency for Healthcare Research and Quality.

Andrade reported having received research funding from Novartis Pharmaceuticals in the past.

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